Abstract
Identification of selective influenza viral sialidase inhibitors is highly desirable in order to minimize or avoid the adverse effects due to the possible inhibition of endogenous human sialidases. We recently reported the evaluation of C9 N-acyl Neu5Ac2en mimetics as probes for human sialidases. Herein, we describe the in vitro activity of the same set of C9 N-acyl Neu5Ac2en mimetics against sialidases expressed by influenza virus A/PR/8/34 (H1N1), A/Memphis/1/72 (H3N2), and A/Duck/313/78 (H5N3) strains. Compound 8 is identified as a promising starting point for the development of viral sialidase selective inhibitors. Multiple sequence alignment and molecular docking techniques are also performed to explore the plausible interaction of compound 8 with viral sialidases.
Highlights
Influenza is a perceivably benign condition that develops in approximately 20% of the world’s population and kills 0.25 to 0.5 million people every year worldwide, according to the WHO [1]
We describe the in vitro activity of the same set of C9 N-acyl Neu5Ac2en mimetics against sialidases expressed by influenza virus A/PR/8/34 (H1N1), A/Memphis/1/72 (H3N2), and A/Duck/313/78 (H5N3) strains
Results expressed as 50% inhibitory concentration (IC50) values are presented in Table 1 together with the previously reported human sialidase inhibitory activities of compounds [39]
Summary
Influenza is a perceivably benign condition that develops in approximately 20% of the world’s population and kills 0.25 to 0.5 million people every year worldwide, according to the WHO [1]. Using the advantage of structure-based drug design method, two potent sialidase inhibitors, Zanamivir 3 (Relenza, GlaxoSmithKline) and an ester prodrug oseltamivir 4 (Tamiflu, Gilead/Roche), were designed and developed for the prevention and the treatment of influenza and were complementing the widespread use of influenza vaccines [24, 25] (Figure 1) Both sialidase (NA) enzyme inhibition and X-ray crystallography studies of these inhibitors suggest that the strategy of designing an inhibitor of NA that binds to the highly conserved active site of the NA achieves the desired goal of activity against all influenza NA subtypes, N1–N9, and influenza B viruses [26, 27]. We report the viral sialidase inhibitory activities and complete experimental details of synthesis and screening of C9 amidelinked hydrophobic analogues
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
